Analysis on HLA haplotypes of loci HLA-A, -B, and -DRB1 in northwest Chinese Han population
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Objective To investigate HLA-A,-B and -DRB1 allele and HLA-A-B,B-DRB1,A-B-DRB1 haplotype frequencies in the northwest Chinese Han population. Methods The authors investigated the HLA-A, -B, -DRB1 allele and haplotype in a northwest Chinese Han population based on 62 families and 101 individuals by use of PCR-sequence specific oligonucleotide probes (PCR-SSOP) DNA typing methods. Results Fifteen alleles for the locus HLA-A, 28 alleles for the HLA-B locus and 13 alleles for the HLA-DRB1 were detected. The results showed that the most frequent HLA alleles found were A02 (0.3244), B13 (0.1200), and DRB1*15 (0.1400). Allele frequencies of more than 10% for HLA antigens were A02, A11, A24, B13, B15, B40, DRB1*04, DRB1*07, DRB1*09, DRB1*15. In the analysis of HLA haplotypes, 122 kinds of HLA-A-B haplotypes and 147 kinds HLA-B-DRB1 haplotypes were found. Two hundred and seventy-eight kinds of HLA-A-B-DRB1 haplotypes were found, comprising 61.78% (278/450) of total theoretical haplotypes. Eighty-three kinds of HLA-A-B-DRB1 haplotypes were shown to have at least two same haplotypes, comprising 18.44% (83/450) of total theoretical haplotypes. The most common HLA-A-B-DRB1 haplotypes were A30-B13-DRB1*07, A02-B46-DRB1*09, A01-B37-DRB1*10, A24-B15-DRB1*15, A02-B46-DRB1*08, A33-B58-DRB1*03. Conclusion The data can be used for the estimation of the probability of finding haplotypically identical, related or unrelated bone marrow donor for an individual patient, and forensic and paternity tests to estimate the frequency of a DNA profile or anthropologic research.Keywords:
HLA-A
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Objective:To analyze HLA-A,B and DRB1 alleles high-resolution polymorphism and haplotypes in the Han population in Jiangsu province.Methods:PCR-SSOP and PCR-SBT methods were applied for HLA high-resolution genotyping of 644 unrelated healthy donors in Jiangsu branch of Chinese National Marrow Donor Program(CMDP) registry.The allele frequencies at HLA-A,B,and DRB1 loci were estimated by direct counting method and the haplotype frequencies were estimated using Arlequin software 3.01.Results:A total of 29 alleles for HLA-A,60 alleles for HLA-B,and 36 alleles for HLA-DRB1 were found.The most common alleles were A*1101(17.86%),B*4601(9.55%)and DRB1*0901(15.76%).The most common A-B-DRB1 haplotype was A*3001-B*1302-DRB1*0701(5.98%),the most common A-B haplotype was A*3001-B*1302(6.68%),the most common B-DRB1 haplotype was B*1302-DRB1*0701(7.22%)and the most common A-DRB1 haplotype was A*3001-DRB1*0701(6.06%).Conclusion:The high-resolution results show the characteristics of HLA distribution in Jiangsu Han population,and it is helpful in HLA matching in transplantation,as well as to population genetics and disease association studies.
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The frequencies of HLA‐A, ‐B, and ‐DRB1 alleles and A‐B‐DRB1 haplotypes were studied in 510 healthy unrelated Koreans, using serological (for A, B) and polymerase chain reaction (PCR)‐single strand conformation polymorphism (for DRB1) methods. A total of 35 DRB1 alleles were detected and the most frequent alleles were DRB1*1302 (10.9%), *0901 (9.5%), *1501 (8.2%), *0803 (7.3%), *0405 (7.3%), *0101 (6.4%), *0406 (6.0%), and *0701 (6.0%). HLA‐DR4 and DR14 groups were most polymorphic, each group composed of eight DRB1 alleles. Two‐locus associations between HLA‐DRB1 and ‐B loci were analyzed. There were 16 A‐B‐DRB1 haplotypes occurring at frequencies of ≥1%, and the five most common haplotypes were A33‐B44‐DRB1*1302 (5.4%), A33‐B58‐DRB1*1302 (3.7%), A33‐B44‐DRB1*0701 (2.9%), A24‐B7‐DRB1*0101 (2.2%), and A24‐B52‐DRB1*1502 (2.0%). Comparison of the distribution of A‐B‐DRB1 haplotypes among East Asian populations revealed that Koreans are closest to Japanese, but show a higher degree of polymorphism compared with Japanese.
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Abstract The frequencies of the human leukocyte antigen alleles HLA‐A, HLA‐B, and HLA‐DRB1 and the A‐B‐DRB1, A‐B, and B‐DRB1 haplotypes were studied in Naxi and Yunnan Han populations using polymerase chain reaction (PCR)‐sequence‐specific amplification for alleles A and B and a PCR‐microtiter plate hybridization method for the DRB1 allele. A total of 8 A, 19 B, and 30 DRB1 alleles were found in the Naxi population, and 15 A, 21 B, and 36 DRB1 alleles were found in Yunnan Han population. The common A‐B‐DRB1 haplotypes in the Naxi population were A*24‐B*15‐DRB1*1202, A*11‐B*15‐DRB1*0405, A*11‐B*15‐DRB1*1202, A*11‐B*38‐DRB1*08032, and A*11‐B*55‐DRB1*0405; the common A‐B haplotypes were A*11‐B*15, A*11‐B*38, and A*24‐B*15; and the common B‐DRB1 haplotypes were B*15‐DRB1*1202, B*38‐DRB1*08032, and B*48‐DRB1*1201. In the Yunnan Han population, the common A‐B‐DRB1 haplotypes were A*24‐B*15‐DRB1*1501, A*24‐B*46‐DRB1*08032, and A*24‐B*15‐DRB1*1201; the common A‐B haplotypes were A*24‐B*15, A*24‐B*46, and A*34‐B*46; and the common B‐DRB1 haplotypes were B*15‐DRB1*1501, B*46‐DRB1*09012, and B*46‐DRB1*1401. Phylogenetic tree and principal component analyzes based on HLA‐A, HLA‐B, and DRB1 allele frequencies suggested that the Naxi ethnic group belongs to the southern Chinese groups, while the Yunnan Han population is a characteristic population located intermediate between northern and southern Chinese groups, although they live in the southwest of China.
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Objective To analyze the sequence and investigate the haplotype diversity of human leukocyte antigen (HLA)-A,B and DRB1 genes in Chinese Han population from Southern China.Methods A total of 421 randomly selected Chinese Han individuals from Southern China were genotyped by polymerase chain reaction (PCR) sequence based typing (SBT) method for HLA-A,B and DRB1 genes,and then the frequencies of allele and haplotype were estimated by maximum-likehood estimation method.Results Twenty-six HLA-A alleles were observed and six common alleles with frequencies higher than 0.05,including A*1101,A*2402,A*0207,A*0201,A*3303 and A*0203,accounted for 78.15% of the total for HLA-A locus. Fifty-three alleles were seen at HLA-B locus,among which,B*4001,B*4601,B*5801,B*1502 and B*1301 were the most frequent,with the frequencies greater than 0.05,and comprised 50.59% of the total. Among the 36 HLA-DRB1 alleles,seven alleles with frequencies greater than 0.05,including DRB1*0901,DRB1*1501,DRB1*1202,DRB1*0803,DRB1*1101,DRB1*0405 and DRB1*0301,accounted for 60.21% of the total HLA-DRB1 alleles. For A-B,B-DRB1 and A-B-DRB1haplotype,there were 372,494 and 1 658 kinds in total respectively. And among them,39,43 and 26 kinds with frequencies higher than 0.005 comprised 66.07%,58.91% and 34.30% of the total haplotypes for each kind,and the most common was A*0207-B*4601,B*4601-DRB1*0901 and A*0207-B*4601-DRB1*0901.Conclusions The allelic frequencies and haplotype diversities at high-resolution level in Chinese Han population from Southern China can provide more insights into the anthropology,forensic medicine,transplantation matching and disease association studies.
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In this study, we used high-resolution DNA typing to investigate the distribution of HLA alleles and haplotypes in Koreans.HLA-A, -B, -C, and -DRB1 alleles were genotyped at the allelic (4-digit) level in 474 healthy Koreans. HLA genotyping was performed in two steps. Initially, serologic typing or generic-level DNA typing was performed using the PCR-sequence-specific oligonucleotide method, and then allelic DNA typing (exons 2 and 3 for class I, and exon 2 for DRB1) was carried out using the PCR-single-strand conformation polymorphism method or sequence-based typing. HLA allele and haplotype frequencies and linkage disequilibrium values were calculated by the maximum likelihood method using a computer program developed for the 11th International Histocompatibility Workshop.A total of 21 HLA-A, 40 HLA-B, 22 HLA-C, and 29 HLA-DRB1 alleles were found in Koreans. The most frequent alleles in each locus with frequencies of ≥ 10% were, in decreasing order of frequency, as follows: A*24:02, A*02:01, A*33:03; B*51:01; C*01:02, C*03:03; and DRB1*09:01. The numbers of two- and three-locus haplotypes with frequencies of >0.5% were as follows: 44 A-C, 42 B-C, 51 A-B, 52 B-DRB1, 42 A-C-B, and 34 A-B-DRB1. Thirteen A-B-DRB1 haplotypes with frequencies of ≥ 1.0% comprised 26.0% of the total haplotypes. The six most common haplotypes were as follows: A*33:03-B*44:03-DRB1*13:02 (3.7%), A*33:03-B*44:03-DRB1*07:01 (3.0%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.8%), A*30:01-B*13:02-DRB1*07:01 (2.3%), and A*11:01-B*15:01-DRB1*04:06 (2.2%).The information obtained in this study can be used as basic data for Koreans in the fields of organ transplantation, disease association, and anthropologic studies.
Linkage Disequilibrium
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The distributions of HLA allele and haplotype are various in the populations. Currently, the data for HLA alleles and haplotypes at three fields resolution level in Chinese Han population is rare. Here, the HLA alleles and haplotypes of the 1734 cord blood samples from Zhejiang Han population, China were reported at three fields resolution. All samples were randomly collected from the Zhejiang Cord Blood Bank, China. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci was genotyped using next generation sequencing method. The genotypes of the samples were assigned using the HLA TypeStream Visual Software version 1.2.0. The frequency of alleles, haplotype estimation and linkage disequilibrium analysis were performed with the Arlequin software 3.5.2.2. It was found that the top three frequent alleles of HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci were A*11:01:01 (25.81%), A*24:02:01 (16.70%), A*02:01:01 (10.61%); B*40:01:02 (15.97%), B*46:01:01 (11.48%), B*58:01:01 (7.96%); C*07:02:01 (19.03%), C*01:02:01 (17.65%), C*03:04:01 (10.41%); DRB1*09:01:02G (17.96%), DRB1*12:02:01 (9.57%), DRB1*08:03:02 (9.54%); DQB1*03:01:01G (21.05%), DQB1*03:03:02 (19.15%), DQB1*06:01:01G (12.08%); DRB4*01:03:01 (25.72%), DRB3*02:02:01 (20.27%), DRB5*01:01:01 (10.96%), respectively. A total of 1528 distinct A∼C∼B∼DRB3/4/5∼DRB1∼DQB1 haplotypes were estimated, and the top three most common haplotypes were A*33:03:01∼C*03:02:02∼B*58:01:01∼DRB3*02:02:01∼DRB1*03:01:01∼ DQB1*02:01:01 (4.02%), A*30:01:01∼C*06:02:01∼B*13:02:01∼DRB4*01:03:01∼ DRB1*07:01:01 ∼DQB1*02:02:01 (3.11%) and A*02:07:01∼C*01:02:01∼B*46:01:01 ∼DRB4*01:03:01∼DRB1*09:01:02G∼DQB1*03:03:02 (3.05%). Some alleles of different HLA loci were shown strong linkage disequilibrium. In conclusion, the data of allele and haplotype of HLA-A, -B, -C, -DRB1, -DQB1 and -DRB3/4/5 loci at three fields resolution level were obtained in Zhejiang Han population, thus contributing to analyze the HLA ploymorphism in the populations.
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ObjectiveTo analyze the polymorphism of HLA-A,B,and DRB1 alleles and their haplotypes in Chinese Man population.Methods Frequencies of HLA-A,B and DRB1 alleles and haplotypes were estimated by maximum-likelihood estimation method based on the genotypes of 2183 Chinese Man bone marrow donors.ResultsA total of 18 HLA-A alleles,44 HLA-B alleles and 15 HLA-DRB1 alleles were detected in Man population,and the most frequent alleles were A*02,A*11,A*24,A*30,A*33,B*13,B*35,B*46,B*51,B*40(B60),B*40(B61),B*15(B62),DRB1*04,DRB1*07,DRB1*08,DRB1*09,DRB1*11,DRB1*12,DRB1*13,DRB1*14 and DRB1*15.A*30-B*13,A*02-DRB1*15,B*13-DRB1*07 and A*30-B*13-DRB1*07 were the most frequent haplotypes in Man population for A-B,A-DRB1,B-DRB1 and A-B-DRB1 haplotype,respectively.The number of haplotypes with frequency ≥ 0.01 for A-B,A-DRB1 and B-DRB1 haplotype was 31,24 and 27,respectively,and ≥ 0.005 for A-B-DRB1 haplotype was 32.There were 14 in A-B,3 in A-DRB1,14 in B-DRB1 and 38 in A-B-DRB1 haploypes that showed strong linkage disequilibrium with ALD≥0.40.ConclusionsThe distribution of HLA-A,B and DRB1 alleles and haplotypes in Man population was similar to that in Northern Chinese Han population.
Linkage Disequilibrium
HLA-B
HLA-A
HLA-DRB1
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Objective To study the polymorphisms of human leukocyte antigen (HLA)-A, B and DRB1 genes and haplotypes at high-resolution level in Northern Chinese Han population. Methods 631 randomly selected Northern Chinese Han individuals were genotyped by polymerase chain reaction-sequence based typing (PCR-SBT) method for their HLA-A, B and DRB1 genes, and then the frequencies of alleles and haplotypes were estimated by maximum-likehood estimation method. Results Thirty HLA-A alleles were observed and five common alleles with frequencies higher than 0.05 which included A * 1101, A * 2402, A* 0207, A * 0201 and A * 3303 accounted for 69.26% of the total for HLA-A locus. Sixty-four alleles were seen at HLA-B locus, and B* 4001,B* 4601,B* 5801 and B* 1502 were the most frequent with frequencies higher than 0.05 which comprised 38.11% of the total. Among the forty-one HLA-DRB1 alleles, seven alleles with frequencies higher than 0.05 included DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0701, DRB1 * 0803, DRB1 * 1101 and DRB1 * 0405, which accounted for 59.98% of the total. 499 A-B, 659 B-DRB1 and 2 426 A-B-DRB1 haplotype were,observed,respectively. 38 A-B, 39 B-DRB1 and 31 A-B-DRB1 haplotypes showed frequencies higher than 0.005 which comprised 59.82%,53.69% and 32.38% of the total. The most frequent haplotype was A * 0207-B * 4601, B * 4601-DRB1 * 0901 and A * 0207-B* 4601-DRB1 * 0901 for each type. Conclusion The presented allelic frequencies and haplotype diversities at high-resolution level in Northern Chinese Han population could be served as reference standard for the anthropology, legal medicine, transplantation matching and disease association studies.
Key words:
Human Leukocyte Antigen, Allele, Haplotype, PCR-SBT, Han Nationality
HLA-A
HLA-B Antigens
Linkage Disequilibrium
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